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Summary: Zuclopenthixol decanoate is a dopamine antagonist licensed for human use to manage schizophrenia and paranoid psychosis. It is in the same drug class (thioxanthene) as fluphenazine decanoate, a drug whose use in horses is reported anecdotally for providing long‐acting sedation. This case study describes severe extrapyramidal signs seen in a Thoroughbred colt after zuclopenthixol decanoate administration. The colt was presented to a referral hospital for an unusual manifestation of colic signs. On admission, the colt began to show clear extrapyramidal neurological signs. The initial suspicion was of fluphenazine decanoate toxicity, which in the limited published literature is treated with intravenous formulations of diphenhydramine hydrochloride and benztropine mesylate. At the time of writing both were unavailable in the United Kingdom without an import license. The closest alternative option, oral diphenhydramine was administered alongside intravenous atropine and pergolide. Improvements in the colt's demeanour and neurological status was noted within 24 h. The colt was hospitalised for a total of 26 days and at time of discharge was clinically normal. Follow‐up communication 3 months after discharge confirmed that the colt had remained neurologically normal. Crucially, toxicology testing submitted to Cornell University was negative for common toxins, including fluphenazine decanoate. Specific secondary testing was performed after suspicion the administration of zuclopenthixol decanoate was raised, which was positive for this compound. Routine drug testing would, therefore, not identify the use of this behaviour modifying drug. Clinical data regarding the use of zuclopenthixol in animals is limited to its use in the translocation of wildlife to relieve stress and aid acclimatisation. To our knowledge, there is no available literature describing the administration of zuclopenthixol decanoate in equine patients. [ABSTRACT FROM AUTHOR]

We report herein that bis(tricyclic) aromatic enes (BAEs) consisting of 6-6-6-membered frameworks such as acridine, xanthene, thioxanthene, and thioxanthene-S,S-dioxide act as a new class of organic luminophores that exhibit blue-to-green fluorescence in the solid state and in polymer film with good to excellent quantum yields. The BAEs were prepared by the palladium-catalyzed double cross-coupling reaction of phenazastannines or 10,10-dimethyl-10H-phenothiastannin with 9-(dibromomethylene)xanthene, 9-(dibromomethylene)thioxanthene, or 9-(dibromomethylene)-9H-thioxanthene-10,10-dioxide. Microcrystals or powder samples of the BAEs exhibited brilliant fluorescence with good to high quantum yields (Φ = 0.45–0.88). Furthermore, more efficient emission of blue-to-green light (Φ = 0.59–0.91) was observed for the BAEs dispersed in the poly(methyl methacrylate) (PMMA) films. Density functional theory (DFT) calculations suggest that the photo-absorption of the (thio)xanthene moiety-containing BAEs proceeds via π–π* transitions, whereas the optical excitation of 10,10-dioxido-9H-thioxanthene moiety-containing BAEs involves an intramolecular charge transfer from the acridine/thioxanthene part to the electron-accepting 10,10-dioxido-9H-thioxanthene moiety. [ABSTRACT FROM AUTHOR]

Herein, we first report an electrochemical methodology for the site-selective alkylation of azobenzenes with (thio)xanthenes in the absence of any transition metal catalyst or external oxidant. A variety of groups are compatible with this electrochemical alkylation, which furnishes the products in moderate to good yields. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) emerges as a critical complication following acute myocardial infarction (AMI) and is associated with a significant increased risk of heart failure, stroke and mortality. Ataxia telangiectasia mutated (ATM), a key player in DNA damage repair (DDR), has been implicated in multiple cardiovascular conditions, however, its involvement in the development of AF following AMI remains unexplored. This study seeks to clarify the contribution of the ATM/p53 pathway in the onset of AF post-AMI and to investigate the underlying mechanisms. The rat model of AMI was established by ligating left anterior descending coronary artery in the presence or absence of Ku55933 (an ATM kinase inhibitor, 5 mg/kg/d) treatment. Rats receiving Ku55933 were further divided into the early administration group (administered on days 1, 2, 4, and 7 post-AMI) and the late administration group (administered on days 8, 9, 11 and 14 post-AMI). RNA-sequencing was performed 14 days post-operation. In vitro, H 2 O 2 -challenged HL-1 atrial muscle cells were utilized to evaluate the potential effects of different ATM inhibition schemes, including earlier, middle, and late periods of intervention. Fourteen days post-AMI injury, the animals exhibited significantly increased AF inducibility, exacerbated atrial electrical/structural remodeling, reduced ventricular function and exacerbated atrial DNA damage, as evidenced by enhanced ATM/p53 signaling as well as γH2AX level. These effects were partially consistent with the enrichment results of bioinformatics analysis. Notably, the deleterious effects were ameliorated by early, but not late, administration of Ku55933. Mechanistically, inhibition of ATM signaling successfully suppressed atrial NLRP3 inflammasome-mediated pyroptotic pathway. Additionally, the results were validated in the in vitro experiments demonstrating that early inhibition of Ku55933 not only attenuated cellular ATM/p53 signaling, but also mitigated inflammatory response by reducing NLRP3 activation. Collectively, hyperactivation of ATM/p53 contributed to the pathogenesis of AF following AMI. Early intervention with ATM inhibitors substantially mitigated AF susceptibility and atrial electrical/structural remodeling, highlighting a novel therapeutic avenue against cardiac arrhythmia following AMI., Competing Interests: Declaration of competing interest The authors declare that there is no competing interest., (Copyright © 2024. Published by Elsevier Inc.)

Comprehensive Summary: By employing a readily available CuCl/DDQ catalyst system, we herein report a direct C(sp3)–H sulfonylation of xanthene derivates with odorless sodium sulfinates. Various 9H‐xanthenes, thioxanthenes, and 9,10‐dihydroacridines are efficiently transformed into the desired benzylic sulfonyl products via a radical/radical cross‐coupling process, proceeding with the merits of broad substrate scope, operational simplicity, good functional group compatibility, and mild reaction conditions. [ABSTRACT FROM AUTHOR]

pH dependent fluorescence emission of a thioxanthone-based probe has been reported recently. The potential determinant factors of pH dependence may provide important clues to design novel thioxanthone-based probes in the future. pH dependence of photochemical kinetics of thioxanthone itself was investigated in this work using nanosecond time-resolved laser flash photolysis. The nanosecond time-resolved transient absorption spectra and kinetics of TX in aqueous acetonitrile were recorded, as well as for a model reaction system including TX with diphenylamine (DPA) as a co-initiator. Besides the well-known absorption peak of 3TX*, other peaks at 417, 518, 673 and 780 nm, have been reliably attributed to major intermediates in the overall reaction between TX and DPA with photolysis, which has been confirmed to occur along a multistep process. In the strong acidic solution (pH≈3.0), TX and protonated TX ions (TXH+) coexist due to protonated equilibrium. Consequently, high proton concentration promotes the predominant decay pathway after photolysis from electron transfer to proton affinity. Subsequently, the different primary products, 3TXH+* or TX•−, proceed different secondary reaction channels. In addition, within the wide pH range from weak acid (pH=5.0) to alkaline solution (pH=13.0), the overall reaction mechanism and rates do not show visible changes. [ABSTRACT FROM AUTHOR]

The photophysical and photochemical behaviors of thioxanthen-9-one (TX) in different solvents have been studied using nanosecond transient absorption spectroscopy. A unique absorption of the triplet state 3TX* is observed, which involves two components, 3nπ* and 3ππ* states. The 3ππ* component contributes more to the 3TX* when increasing the solvent polarity. The self-quenching rate constant ksq of 3TX* is decreased in the order of CH3CN, CH3CN/CH3OH (1:1), and CH3CN/H2O (1:1), which might be caused by the exciplex formed from hydrogen bond interaction. In the presence of diphenylamine (DPA), the quenching of 3TX* happens efficiently via electron transfer, producing the TX·− anion and DPA·+ cation radicals. Because of insignificant solvent effects on the electron transfer, the electron affinity of the 3nπ* state is proved to be approximately equal to that of the 3ππ* state. However, a solvent dependence is found in the dynamic decay of TX·– anion radical. In the strongly acid aqueous acetonitrile (pH=3.0), a dynamic equilibrium between protonated and unprotonated TX is definitely observed. Once photolysis, 3TXH+* is produced, which contributes to the new band at 520 nm. [ABSTRACT FROM AUTHOR]

Readily accessible 2‐aryloxybenzaldehydes and 2‐(arylthio)benzaldehydes undergo a sequence of reactions leading to a wide variety of unsubstituted 9H‐xanthenes and thioxanthenes in high yields when heated with a Lewis acid in diisopropyl ether. This reductive cyclization method is compatible with several important functional groups. The method is also applicable for the selective reductive cyclization of the more electron‐rich aryl ring of a 2,6‐bis(aryloxy)benzaldehyde. The key feature of this transformation is the chemoselective reduction of a transient xanthylium ion in the presence of aldehydic group via intermolecular hydride transfer from diisopropyl ether (solvent). [ABSTRACT FROM AUTHOR]

The rising tide of antibacterial drug resistance has given rise to the virtual elimination of numerous erstwhile antibiotics, intensifying the urgent demand for novel agents. A number of drugs have been found to possess potent antimicrobial action during the past several years and have the potential to supplement or even replace the antibiotics. Many of these ‘non-antibiotics’, as they are referred to, belong to the widely used class of neuroleptics, the phenothiazines. Another chemically and pharmacologically related class is the thioxanthenes, differing in that the aromatic N of the central phenothiazine ring has been replaced by a C atom. Such “carbon-analogues” were primarily synthesized with the hope that these would be devoid of some of the toxic effects of phenothiazines. Intensive studies on syntheses, as well as chemical and pharmacological properties of thioxanthenes, were initiated in the late 1950s. Although a rather close parallelism with respect to structure activity relationships could be observed between phenothiazines and thioxanthenes; several thioxanthenes were synthesized in pharmaceutical industries and applied for human use as neuroleptics. Antibacterial activities of thioxanthenes came to be recognized in the early 1980s in Europe. During the following years, many of these drugs were found not only to be antibacterial agents but also to possess anti-mycobacterial, antiviral (including anti-HIV and anti-SARS-CoV-2) and anti-parasitic properties. Thus, this group of drugs, which has an inhibitory effect on the growth of a wide variety of microorganisms, needs to be explored for syntheses of novel antimicrobial agents. The purpose of this review is to summarize the neuroleptic and antimicrobial properties of this exciting group of bioactive molecules with a goal of identifying potential structures worthy of future exploration.

A new method for the one‐step C−H amination of xanthene and thioxanthene with sulfonamides is reported, without the need for any metal catalyst. A benzoquinone was employed as a hydride (or two‐electron and one‐proton) acceptor. Moreover, a previously unknown and uncatalyzed reaction between iminoiodanes and xanthene, thioxanthene and dihydroacridines (9,10‐dihydro‐9‐heteroanthracenes or dihydroheteroanthracenes) is disclosed. The reactions proceed through hydride transfer from the heteroarene substrate to the iminoiodane or benzoquinone, followed by conjugate addition of the sulfonamide to the oxidized heteroaromatic compounds. These findings may have important mechanistic implications for metal‐catalyzed C−H amination processes involving nitrene transfer from iminoiodanes to dihydroheteroanthracenes. Due to the weak C−H bond, xanthene is an often‐employed substrate in mechanistic studies of C−H amination reactions, which are generally proposed to proceed via metal‐catalyzed nitrene insertion, especially for reactions involving nitrene or imido complexes that are less reactive (i.e., less strongly oxidizing). However, these substrates clearly undergo non‐catalyzed (proton‐coupled) redox coupling with amines, thus providing alternative pathways to the widely assumed metal‐catalyzed pathways. [ABSTRACT FROM AUTHOR]

Abstract Four novel spiro[fluorene-9,9'-thioxanthene] core based wide-energy-gap compounds Cz-S, 2Cz-S, Cz-SO2, and 2Cz-SO2 were developed as host materials for a general thermally activated delayed fluorescence (TADF) emitter (4s, 6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (4CzIPN). The excited states of the sulfane-containing Cz-S and 2Cz-S are in local emission (LE) states while those of the sulfonyl-containing Cz-SO2 and 2Cz-SO2 are in charge transfer (CT) states. The device based on 2Cz-S exhibits the highest efficiency among them with a maximal current efficiency (CE) of 52.1 cd/A and a maximal external quantum efficiency (EQE) of 16.5% due to the largest radiative triplet exciton utilization capacity through intersystem crossing from T 1 to S 1. In addition, the devices based on Cz-SO2 and 2Cz-SO2 exhibit obviously reduced efficiency roll-off due to their improved carrier balance in a wide current density range, and their J 0 (the current density at the half maximum of the EQE) values reach as high as 93 and 115 mA/cm2. It is also of interest their EL spectra are independent on the host dipole moment due to the spiro-conformation that may reduce the interaction between host and dopant. Highlights • Four spiro[fluorene-9,9'-thioxanthene] core derived compounds were developed as the host of TADF emitter 4CzIPN. • The bipolar characteristic of the hosts can be acquired via changing the valence of sulfur atom. • Bipolar hosts can reduce efficiency roll-off while don't change their EL spectra. [ABSTRACT FROM AUTHOR]

Thioxanthones are bioisosteres of the naturally occurring xanthones. They have been described for multiple activities, including antitumor. As such, the synthesis of a library of thioxanthones was pursued, but unexpectedly, four tetracyclic thioxanthenes with a quinazoline–chromene scaffold were obtained. These compounds were studied for their human tumor cell growth inhibition activity, in the cell lines A375-C5, MCF-7 and NCI-H460. Photophysical studies were also performed. Two of the compounds displayed GI50 values below 10 µM for the three tested cell lines, and structure–activity relationship studies were established. Three compounds presented similar wavelengths of absorption and emission, characteristic of dyes with a push-pull character. The structures of two compounds were elucidated by X-ray crystallography. Two tetracyclic thioxanthenes emerged as hit compounds. One of the two compounds accumulated intracellularly as a bright fluorescent dye in the green channel, as analyzed by both fluorescence microscopy and flow cytometry, making it a promising theranostic cancer drug candidate.

Abstract Chlorprothixene (CPTX) is an antipsychotic drug of the thioxanthene class. Although it is widely used as a tranquillizer in psychiatry, anesthesiology, pediatrics, and in general medical practice, there is a gap in knowledge regarding its occurrence and fate in the environment. Therefore, we provide for the first-time data on the environmental fate and ecotoxicity of CPTX and its potential photo-transformations products (PTPs). Firstly, two standardized biodegradation tests (Closed Bottle test (CBT) and Manometric Respiratory test (MRT)) were performed to assess CPTX's environmental biodegradability. Then, its photodegradability was studied using Xenon and UV lamps. Effects of different conditions (initial drug concentration, pH, and temperature) were applied during UV-photodegradation. Subsequently, the time courses of CPTX and dissolved organic carbon (DOC) concentrations were monitored throughout the photodegradation tests. After that, high-resolution mass spectrometry was employed to elucidate the structures of the formed photo-transformation products (PTPs). In addition, biodegradation tests were performed for the photolytic mixtures to assess the biodegradability of the PTPs. Finally, the (eco)toxicity assessment for CPTX and its photolytic mixtures was predicted using different (quantitative) structure-activity relationship ((Q)SAR) software. CPTX was found to be not readily biodegradable in CBT and MRT. CPTX was not eliminated by irradiation with the Xenon lamp, however primarily eliminated using the UV-lamp. The CPTX elimination during UV-irradiation was faster at lower concentrations. CPTX UV-photodegradation was affected by pH value, while not affected by the temperature of the irradiated solution. 13 PTPs were detected in UV-photolysis mixtures. One additional product was detected in CPTX standard solution, and it was degraded simultaneously with CPTX during UV-irradiation. On one hand, Biodegradation assays revealed that UV-photolytic mixtures of CPTX, containing its PTPs, were not better biodegradable than CPTX itself. On the other hand, LC-MS analysis showed some PTPs which were eliminated after the biodegradation tests indicating possible biodegradability of these PTPs. This because those PTPs are present in low concentrations in the photolysis mixture and their effect can be hindered by the effect of CPTX and other non-biodegradable PTPs. QSAR analysis revealed that CPTX and some of its PTPs may have some human and/or eco-toxic properties. In conclusion, the release of CPTX into aquatic environments could be harmful. Therefore, further research focusing on CPTX and its PTPs are strongly recommended. Graphical abstract Image 1 Highlights • Chlorprothixene (CPTX) is not readily biodegradable in the aquatic environment. • CPTX degraded by UV-irradiation and 13 unknown photo-products (PTPs) were produced. • CPTX main UV-degradation pathway is hydroxylation with or without de-chlorination. • LC-MS analysis of biodegradation samples showed 6 PTPs as probably biodegradable. • Toxicity assessment showed possible toxic properties for CPTX and some of its PTPs. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Tetraarylmethanes prepared with all phenyl groups and diverse substitution. • Friedel-Crafts cyclization gives 9,9-diarylthioxanthene precursors. • Tetraarylmethanes obtained by desulfurization with Raney nickel. • Tetraarylmethanes with electron-withdrawing or electron-donating groups. • Nucleophilic addition to benzophenone to form triarylmethanols. Abstract Tetraarylmethanes are an important class of molecules that contain four aryl groups bonded to a central carbon atom. The shape/three-dimensionality of these molecules makes them suitable for organic light-emitting diodes (OLEDs), organic solar cells, hydrogen storage, and even drug-delivery. Despite their importance, there are only a few methods available for their preparation. Herein, we report a simple procedure for the preparation of tetraarylmethanes that involves a bismuth-catalyzed Friedel-Crafts cyclization followed by a desulfurization reaction mediated by Raney nickel. [ABSTRACT FROM AUTHOR]

An efficient organocatalytic route has been developed to synthesize novel substituted thioxanthenes (2a-2v) starting from diaryl thioether alcohols (1a-1v) using the intramolecular Friedel-Crafts reaction. The starting materials were obtained in two stages via a coupling reaction followed by the Grignard reaction. In this study, we tried for the first time to use some organic Brønsted acids as organocatalysts (3a-3h) in the intramolecular Friedel-Crafts cyclization reaction of thioether alcohols. The synthesis of original substituted thioxanthenes was achieved within 15 minutes by using N-triflylphosphoramide (3h) with quantitative yields in THF at room temperature. [ABSTRACT FROM AUTHOR]

Abstract A set of conjugated polymers PCzDPTx with carbazole/diphenylamine as backbone and 9 H -thioxanthen-9-one-10,10-dioxide as the pendant, where DPT is 2-(4-(diphenylamino)-phenyl)-9 H -thioxanthen-9-one-10,10-dioxide, and x = 1, 5, 10, 25 and 50, respectively, and two alternating copolymers PTCz and PTD with the backbone consisting of the acceptor unit 9 H -thioxanthen-9-one-10,10-dioxide and the donor unit carbazole and diphenylamine groups have been respectively synthesized by Pd-catalyzed Suzuki coupling polycondensation. These polymers in films show long wavelength emissions of 573–629 nm with thermally activated delayed fluorescence (TADF) characteristics, confirmed by theory calculations and their transient PL decay spectra. Various organic light-emitting diodes (OLEDs) using the TADF polymers as emitters were fabricated by solution processing. The doped OLEDs based on the polymers PTD and PCzDPT50 with the 50% molar content of the DPT unit as the emitters produce the saturated red electroluminescence with Commission Internationale de l'Eclairage (CIE) coordinates (0.64, 0.36) and (0.63, 0.37), respectively. For the first time, a TADF polymer based sensitizer was utilized to further improve the electroluminescent performances of the TADF polymers with low quantum yields, e.g., at the maximum, 3.8-fold increase in the brightness and 1.8-fold increase in the external quantum efficiency were simultaneously demonstrated. Graphical abstract Image 1 Highlights • A series of red light-emitting polymers featuring thermally activated delayed fluorescence (TADF) are reported. • The color can be easily tuned by changing the concentration of the TADF moiety. • Saturated red emission with the peak wavelength of 670 nm is achieved with the TADF copolymer. • The scheme of TADF polymer sensitized TADF polymer is adopted for the first time. [ABSTRACT FROM AUTHOR]

2‐[Bis(4‐amino(nitro)phenyl)aminomethyl]‐9H‐thioxanthene‐9‐ones and their S‐oxide derivatives have been synthesized, and their electrochemical reduction (ECR) in N,N‐dimethylformamide (DMF) and MeCN has been studied by cyclic voltammetry (CV). The thioxanthene‐9‐one group [Th(O)S] and thioxanthene‐9‐one S‐dioxide group [Th(O)SO2] determine the first one‐electron peak potentials of 2‐[bis(4‐aminophenyl)aminomethyl]‐9H‐Th(O)S/Th(O)SO2. The first peak potentials of the corresponding dinitro compounds are determined by the ratio of reduction potentials of bis(4‐nitrophenyl)amino and 9H‐thioxanthene‐9‐ones moieties. Radical anions (RA) of the synthesized compounds have been obtained by ECR in DMF and MeCN and characterized by EPR spectroscopy together with DFT calculations at the (U)B3LYP/6‐31 + G/PCM level of theory. Th(O)S and Th(O)SO2 groups are thermally stable up to 270 °C. The synthesized 2‐[bis(4‐aminophenyl)aminomethyl]‐9H‐Th(O)S/Th(O)SO2 are electrochemically active monomers for subsequent synthesis of the corresponding electroactive polyimides with thioxanthene‐9‐one based pendant groups for their applications in the design of nonvolatile memory storage devices. The pendant groups are characterized by low redox potentials and reversibility towards electron transfer. [ABSTRACT FROM AUTHOR]

In the “cycloketyl radical mediated living polymerization” (CMP) process, a cycloketyl compound, [9,9′]bixanthenyl-9,9′diol (BIXAN) was ultilized as initiator and mediator. The cycloketyl (CK) radical was used as the dormant radical to achieve the increase of molecular weight. Herein, a series of cycloketyl thioketones were synthesised by Lawesson’s reagent by one step reaction with high yeild, and we found that, when a special cycloketyl thioketone compound, thioxanthene-9-thione (TXT), was added to a routine radical polymerization system, TXT could capture chain radical, and simultaneously formed an radical analogous to CK radical in structure, which could trigger the growth of polymer chains. This simple system was efficient to initiate the polymerization of methyl methacrylate (MMA) and in all cases the molecular weights increased with the increase of conversions. By the end-group analysis with 1H-NMR and MALDI-TOF MS, it was confirmed that the P-STXT radical was used to control the polymerization. The re-initiating reactions were achieved when PMMA was used as the macro-initiator. [ABSTRACT FROM AUTHOR]

Self-assembled silver nanoparticles (Ag NPs) on calf thymus DNA (ct-DNA) chains were synthesized in the presence of 2-mercaptothioxanthone (TX-SH) by use of UV irradiation technique. Thioxanthone itself and its derivatives show interesting photochemical and biological properties. The formation of Ag NPs on the ct-DNA was achieved with and without TX-SH as a thioxanthone derivative photoinitiator which played a photoreducing role for the formation of Ag NPs. The photoreducing reaction of Ag ions to Ag NPs was followed by UV–vis absorption spectroscopy. A new band was observed at 428 nm which was a good sign of the surface plasmon resonance (SPR) of Ag NPs. Fluorescence quenching was effectively observed depending on the irradiation time of the solution, possibly as a result of Ag NPs size. Particle size analysis and Scanning Electron Microscopy (SEM) imaging confirmed the size of the formed Ag NPs and silver nanoclusters (Ag NCs) effectively. In this study, we report for the first time the formation of self–assembled Ag NPs on ct-DNA in the presence of 2-mercaptothioxanthone by photoirradiation technique. TX-SH played two important roles; photoreducing and photostabilizing agent for the formation of Ag NCs on ct-DNA. Fluorophore character of synthesized Ag NPs on DNA may help to develop new techniques for biological and medical aspects. [ABSTRACT FROM AUTHOR]